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The impact of the structure and organization of clinical research services (data management model) on the workload of clinical research coordinators (CRCs) at investigative sites is undocumented. This paper describes three types of data management models and their potential influence on the workload of CRCs. A 20-item survey, covering information about accrual to clinical trials, staflng levels, use of workload measurement tools, and the data management model, was e-mailed to nine CRCs working at selected cancer centers in the United States.Six CRCs representing four university-based institutions and two community hospitals responded. StafJig levels and number of patients placed on clinical trials varied by institution and data management model. One out of six centers used a workload formula based upon the time it takes to complete a task. The centralized clinical data managemenr model and the modifiedhixed models were common. Our findings suggest that it is important to understand the structure of the clinical data management model, among other factors, in evaluating the workload of CRCs.

The site at which anaesthetics act within the central nervous system (CNS) has been the subject of research for almost 100 years. Most success has been obtained in defining the physical nature of the site [70]. For example, the well established correlation of anaesthetic potency to fat solubility indicates that the site of action is hydrophobic. Research using anaesthetics with unusual solubility properties (sulphur hexafluoride and carbon tetrafluoride) failed to provide support for the alternative hypothesis that interaction within the aqueous phase of the CNS was responsible for anaesthesia [45,46]. It is now generally agreed that interaction at a hydrophobic site is involved, but debate continues as to whether or not this is within the membrane lipids or at a hydrophobic region within specific proteins. Evidence for the latter view has been provided by the fact that bacterial and firefly luciferases are sensitive to anaesthetics with potency ratios comparable to those of mammalian anaesthesia [21, 22, 32, 42, 43]. However, there is no evidence for a substance related to the luciferases within the mammalian CNS and for the protein model of general anaesthesia to be advanced such a target site must be identified. General anaesthetics may affect signal transmission by altering action potential propagation or synaptic transmission or, indeed, both. At clinically relevant concentrations, general anaesthetics appear primarily to affect synaptic processes [5, 53, 58-61], although impulse conduction in small unmyelinated fibres is reduced [4]. There is some evidence that anaesthetics may inhibit neurotransmitter release also [56], which if it were to occur at an excitatory synapse could produce the necessary depression of synaptic transmission. Anaesthetics also have effects on the postsynaptic neurotransmitter receptor/ion channel complex. Much of the early work concentrated on the nicotinic acetylcholine receptor as a model for ligand-gated ion channels in general. However, attention is now being devoted to the receptors activated by excitatory amino acids, which probably form the majority of the fast excitatory synapses in the CNS, and to the principal inhibitory receptors, activated by yaminobutyric acid (GABA) and glycine.

Sodium phenylbutyrate is a biological-response modifier that acts as a dose-dependent inhibitor of glioma cell proliferation, migration, and invasiveness in vitro, possibly by inhibition of urokinase and c-myc pathways. Despite its biological activity in vitro, there have not been any prior reports of efficacy in the treatment of human malignant gliomas. We report a 44-year-old female with a recurrent, multicentric, malignant glioma who experienced a durable remission lasting more than four years. The patient initially presented with seizures caused by a biopsy-proven anaplastic astrocytoma of the frontal lobe. The patient was treated with radiation therapy and Procarbazine-CCNU-Vincristine (PCV). However, the tumor progressed and extended to the corpus callosum with midline shift, refractory to four cycles of continuous 72-h infusion of BCNU/Cisplatinum. Additional enhancing lesions appeared in the left frontal and left temporal lobes. The patient was started on sodium phenylbutyrate, 18 g daily in three divided oral doses, and reduced to 9 g/day and eventually to 4.5 g/day to eliminate mild, reversible side effects. Four years later, the patient has a KPS functional score of 100%. Phenylbutyrate is a well-tolerated, oral agent that shows potential for the treatment of malignant gliomas. Further studies should be considered to identify a subset of patients that have tumors sensitive to phenylbutyrate, either as a single agent or in combination with radiation therapy or other chemotherapeutic agents.